The US population is becoming obese, which in turn is increasing the incidence of many chronic diseases. Emerging information suggests a strong association between obesity and increased risk for hepatocellular carcinoma (HCC). Adipose tissue is a source of chronic low-level inflammatory cytokines and recent work suggests that inflammation acts as a promoter to enhance liver cancer. Broccoli contains precursors to sulforaphane, which has both anti- inflammatory and anti-carcinogenic properties, as well as indole-3-carbinol, which has some anti-carcinogenic properties. Yet there are no studies of prevention of obesity-derived inflammation or HCC by dietary broccoli or broccoli sprouts. We hypothesize that whereas diet-induced obesity speeds the development of diethylnitrosamine (DEN)-induced HCC, incorporation of broccoli, and to a lesser extent, broccoli sprouts in the diet will counter the impact of obesity by inhibiting inflammation and carcinogenesis. Specifically, we aim to: 1) establish the high fat diet (HFD)-induced DEN mouse model of HCC and follow development through preneoplasia to carcinoma formation, 2) evaluate the impact of whole, freeze-dried broccoli, broccoli sprouts (containing no indoles), broccoli sprouts plus indole-3-carbinol (I3C), I3C alone or no additions, on preneoplasia and on HCC. The significance of this work is that it will show if broccoli, with both sulforaphane and indoles, is more or less effective than broccoli sprouts, when the two are balanced for dietary provision of sulforaphane. Most work in this area focuses on sulforaphane and broccoli sprouts, a few laboratories focus on indole-3-carbinol, but very little is known about the impact of the whole vegetable, broccoli, the most common component in our diet. PUBLIC HEALTH RELEVANCE: Obesity in America is increasing annually and is associated with an increased risk for liver cancer. Yet very few studies have looked at dietary control of this - and no studies have looked at the impact of the anti-carcinogenic food broccoli. Here we propose to establish a model of dietary obesity-enhanced liver cancer and gain preliminary data on a comparison between the impact of broccoli and broccoli sprouts on obesity-induced inflammation, preneoplasia and hepatocellular carcinoma.